Metformin for Exercise Capacity
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of Virginia
Must not be taking: Metformin, Insulin, GLP-1, SGLT-2
Disqualifiers: Type 1 or 2 diabetes, Smoking, Severe liver or kidney disease, others
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?
Metformin is the most prescribed blood sugar (glucose)-lowering medication for patients diagnosed with type 2 diabetes mellitus (T2DM). Metformin stimulates glucose uptake in skeletal muscle similar to the effects of exercise, though, some studies report that metformin may decrease exercise capacity. The main question this study looks to answer is: • Does metformin alter exercise capacity? Participants will: * Complete 5 exercise tests on a stationary bike. * Undergo a body composition test. * Take metformin and placebo. * Complete food and symptom logs. The researchers hypothesize that: • Metformin will reduce aerobic capacity.
Will I have to stop taking my current medications?
The trial requires that participants do not use medications that significantly alter glucose regulation, such as metformin, insulin, or similar drugs. If you are taking any of these, you would need to stop before participating.
What evidence supports the effectiveness of the drug metformin for improving exercise capacity?
Research shows that metformin can enhance anaerobic capacity (the ability to perform short bursts of high-intensity exercise) and increase the time to exhaustion in rats, although it does not improve aerobic capacity (endurance). Additionally, metformin may protect muscles from exercise-induced damage, which could be beneficial for maintaining muscle health during physical activity.12345
Is metformin generally safe for humans?
How does the drug metformin differ from other treatments for improving exercise capacity?
Metformin is unique because it may protect muscles from exercise-induced damage and improve metabolic efficiency during intense exercise, unlike other treatments that primarily focus on enhancing performance directly. It is commonly used for type 2 diabetes but shows potential benefits for exercise capacity by affecting muscle adaptation and reducing perceived exertion.13589
Eligibility Criteria
This trial is for healthy, active adults aged 18-30 who have never taken Metformin, with a BMI under 30. Women must be premenopausal with regular menstrual cycles and all participants should be able to follow the study schedule.Inclusion Criteria
I am between 18 and 30 years old.
I have never taken Metformin.
My BMI is under 30.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 day
1 visit (in-person)
Treatment
Participants undergo a 19-day treatment phase with metformin and placebo, including exercise tests and body composition assessments
19 days
Multiple visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Metformin (Anti-diabetic agent)
Trial OverviewThe study tests whether Metformin affects exercise capacity in young adults. Participants will take both Metformin and a placebo at different times, complete bike exercises, body composition tests, and keep track of their food intake and any symptoms.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Metformin (MET)Experimental Treatment1 Intervention
At the end of the screening visit, participants will be randomized to either Condition A or Condition B (MET or PL first). Participants will begin the 19-day treatment phase of study the day after screening.
During each treatment phase, participants will consume metformin as follows: 1x500 mg tablet/day for 5 days, 2x500 mg tablets/day for 5 days, and 3x500 mg tablets/day (or maximally tolerated dosage) for 9 days.
Participants will then complete a VO2peak/LT test on day 16, rest for 48 hours, then complete a time-to-exhaustion test (day 19) during the final days of the treatment phase. After the time-to-exhaustion test, participants will begin the placebo treatment phase.
Group II: Placebo (PL)Placebo Group1 Intervention
At the end of the screening visit, participants will be randomized to either Condition A or Condition B (MET or PL first). Participants will begin the 19-day treatment phase of study the day after screening.
During each treatment phase, participants will consume placebo as follows: 1x500 mg tablet/day for 5 days, 2x500 mg tablets/day for 5 days, and 3x500 mg tablets/day (or maximally tolerated dosage) for 9 days.
Participants will then complete a VO2peak/LT test on day 16, rest for 48 hours, then complete a time-to-exhaustion test (day 19) during the final days of the treatment phase. After the time-to-exhaustion test, participants will begin the metformin treatment phase.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of VirginiaCharlottesville, VA
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Who Is Running the Clinical Trial?
University of VirginiaLead Sponsor
References
Effect of metformin on exercise capacity: A meta-analysis. [2018]Label="AIMS" NlmCategory="OBJECTIVE">To evaluate the effect of metformin on various parameters of exercise capacity [oxygen consumption (VO2), peak oxygen consumption (VO2peak), heart rate (HR), exercise test duration, respiratory exchange ratio (RER), rating of perceived exertion (RPE), lactate and ventilatory anaerobic threshold (VAT)].
Chronic metformin intake improves anaerobic but not aerobic capacity in healthy rats. [2020]The effect of chronic metformin intake on aerobic and anaerobic capacity was examined in healthy rats. Twenty rats completed 10 days of metformin (MET) ingestion (250 mg). After this period, the animals performed four high-intensity bouts until exhaustion at 9%, 11%, 13%, and 15% of body mass (BM) in swimming, separated by 24 h, with prior metformin (250 mg) or placebo (PL). The critical load (CL) and anaerobic work capacity (AWC - W') were calculated and considered aerobic and anaerobic capacity, respectively. There was no difference in CL between the MET and PL groups (p > 0.05). The AWC - W' was higher in the MET group than in the PL group (p = 0.004). Time until exhaustion (seconds) at all bouts were higher (p < 0.004) in the MET group (9% of BM = 434.5 ± 267.3, 11% of BM = 269.6 ± 214.2, 13% of BM = 174.0 ± 40.9, 15% of BM = 146.6 ± 15.9) compared to the PL group (9% of BM = 96.4 ± 22.3, 11% of BM = 65.5 ± 13.4, 13% of BM = 51.1 ± 5.5, 15% of BM = 40.8 ± 7.5). Glucose concentration was higher at 90 and 120 min than at 0 and 30 min for the MET group (intragroup) during the oral glucose test tolerance; there was no difference between the MET and PL groups for area under curve. MET ingestion enhances AWC - W' and times to exhaustion but not aerobic capacity.
Does metformin modify the effect on glycaemic control of aerobic exercise, resistance exercise or both? [2022]Some previous studies suggested that metformin might attenuate the effects of exercise on glycaemia or fitness. We therefore examined whether metformin use influenced changes in glycaemic control, fitness, body weight or waist circumference resulting from aerobic and/or resistance training in people with type 2 diabetes participating in an exercise intervention trial.
The Effect of Metformin on Self-Selected Exercise Intensity in Healthy, Lean Males: A Randomized, Crossover, Counterbalanced Trial. [2022]Label="Introduction">In general, patients with type 2 diabetes have lower cardiorespiratory fitness levels and perform exercise at lower intensities compared to healthy controls. Since metformin (MET) has been shown to increase the rate of perceived exertion (RPE) during exercise with a fixed intensity, MET per se may reduce self-selected exercise intensity. The aim of this study was to assess the effect of MET on self-selected exercise intensity.
Metformin Protects Rat Skeletal Muscle from Physical Exercise-Induced Injury. [2023]Metformin (Met) is a drug commonly prescribed in type 2 diabetes mellitus. Its efficacy is due to the suppression of hepatic gluconeogenesis, enhancement of peripheral glucose uptake and lower glucose absorption by the intestine. Recent studies have reported Met efficacy in other clinical applications, such as age-related diseases. Despite the wide clinical use of Met, its mechanism of action on muscle and its effect on muscle performance are unclear. We investigated the effects of Met combined with training on physical performance (PP) in healthy rats receiving Met for 8 weeks while undergoing daily moderate exercise. We evaluated the following: PP through graded endurance exercise test performed before the beginning of the training protocol and 48 h before the end of the training period; blood ALT, AST, LDH and CK-MB levels in order to address muscle damage; and several blood and muscle myokines and the expression of factors believed to be involved in muscle adaptation to exercise. Our data demonstrate that Met does not improve the positive effects of exercise on performance, although it protects myocytes from exercise-induced damage. Moreover, given that Met positively affects exercise-induced muscle adaptation, our data support the idea of the therapeutic application of Met when muscle function and structure are compromised.
Clinical development of metformin extended-release tablets for type 2 diabetes: an overview. [2013]Glumetz (Depomed, Inc., Menlo Park, CA, USA) is a recently approved gastric retentive extended-release formulation of metformin (M-ER) that provides effective, sustained and well-tolerated glycemic control with once daily administration. Pharmacokinetic studies have demonstrated a similar bioavailability of M-ER administered once daily to immediate-release metformin given twice daily. In addition, M-ER has demonstrated a nearly linear dose proportionality with a relative bioavailability of highest dose to lowest dose of 80%, whereas with immediate-release metformin the relative bioavailability of the highest dose to the lowest dose is only 58%. M-ER demonstrated a positive food effect and should be administered with a meal, preferably the evening meal. Because metformin is only eliminated through renal mechanisms, the use of M-ER, as is the case with other formulations, is contraindicated in patients with renal impairment. Administration of M-ER with sulfonylureas (SUs) had no effect on the pharmacokinetics of metformin. In controlled clinical trials M-ER demonstrated efficacy for 24 weeks as a monotherapy or in combination with SU. Additionally, glycemic control was maintained for an extra 24 weeks in an open-label monotherapy extension study of M-ER. M-ER was well tolerated in all studies.
Metformin extended release for the treatment of type 2 diabetes mellitus. [2019]Metformin extended release (ER) (Glumetza, Depomed, Inc.) is a recently approved formulation that provides effective and well-tolerated glycaemic control with once-daily dosing. Metformin ER has similar bioavailability to conventional immediate-release (IR) formulations. In controlled clinical trials, metformin ER provided effective glycaemic control for 24 weeks when administered either as monotherapy or in combination with sulfonylurea. Good glycaemic control was maintained for an additional 24 weeks during an open-label extension study. Once-daily dosing with metformin ER 1500 mg/day was as effective as twice-daily dosing with metformin IR at the same total daily dose. Metformin ER was well tolerated at doses of 1500 or 2000 mg/day, with no increase in the frequency or severity of adverse events at the higher dose.
Metformin anticipates peak of lactate during high-intensity interval training but no changes performance or neuromuscular response in amateur swimmers. [2022]Metformin demonstrated potential to improve metabolic efficiency in short-intense and prolonged-continuous efforts. The present study investigates the acute effects of metformin intake on performance, rating of perceived exertion (RPE), blood lactate, blood glucose and neuromuscular parameters related to swimming high-intensity interval series.
The effect of metformin treatment on volumes of free-living physical activity and sedentary behaviour: A post-hoc analysis of the PRE-D trial. [2023]Perceived physical exertion is increased when exercise is performed on metformin treatment, but the clinical relevance of this is unknown. In this post hoc analysis of a randomized, controlled trial, we investigated whether metformin treatment was associated with lower levels of free-living physical activity.   Ninety individuals with overweight/obesity (BMI>25 m2/kg) and HbA1c-defined prediabetes (39-47 mmol/mol) were randomized to treatment with dapagliflozin (SGLT2-inhibitor; 10 mg once daily, n=30), metformin (850 mg twice daily, n=30) or no treatment (control, n=30) for 13 weeks in a parallel-group, open-label trial. Before (baseline), during (6 weeks) and immediately after (13 weeks) cessation of treatment, a 6-day assessment of physical activity and sedentary behaviour was performed using accelerometer-based physical activity monitors. Intention-to-treat analyses revealed no within-group changes or differences in change between the groups for any measures of physical activity or sedentary behaviour at neither 6 nor 13 weeks. Short-term metformin treatment does not reduce free-living physical activity level in individuals with overweight/obesity and HbA1c-defined prediabetes.